Background

Orofacial clefts (OFC) occur in 1.7 per 1,000 live births with more than 10,000 infants born with clefts in Europe each year and with marked variation both in birth prevalence and standards of care. All individuals require multi-disciplinary care from birth until adulthood and have higher morbidity and mortality throughout life than unaffected persons, and there is a burden to their families and to society. This Network aims to deal with the 2 major themes, treatment (quality of care) and prevention (via genetics and environmental factors), in conjunction with the recently formed European Cleft Organisation (ECO) who have begun to address the health inequalities with particular focus on Eastern Europe.

This ESF EUROCleftNet Network proposal will build on previous success of collaborative research in the field of non-syndromic OFC (NS-OFC). The recent GWAS “phase” of research in the field has spawned a comprehensive list of putative genetic loci, and the new grand challenges are (a) to fine map the cleft loci and identify the functional gene variants that are at the base of the genetic risk for NS-OFC (b) embark on epigenetic and functional genomics projects (c) undertake gene-environment interaction studies, (d) unravel the epistatic interactions that are part of the aetiology of NS-OFCs and (e) translate genetic findings into clinical practice and prevention strategies.

The aim is to develop biomarkers to measure nutritional and lifestyle interventions in prevention, produce a panel of gene loci that could be screened for risk assessment in the clinical setting and ultimately progress to recommendations for prevention. Expertise in statistical approaches, the availability of high throughput genome wide techniques, the triad DNA biobank already collected through EUROCRAN, robust data on phenotyping, combined with the diversity of the European populations give the EUROCleftNet scientists a leading start in this project.